In order to provide a scientific basis for possible therapeutic approach to human spinal cord injury, animal (rat) trials with multiple classifications of agents will be continued during the year, including calcium entry blockers, steroids, hyperbaric oxygen, and antioxidants. In addition, therapeutic trials with phosphate and other buffers will be continued. Therapeutic trials will, at the same time, test various hypotheses concerning primary and secondary injury factors in the production of necrosis following traumatic injury. These include calcium toxicity, ischemia and free radical injury. Lactic acid myelopathy in vivo developed during the last grant period will be evaluated to determine the extracellular pHs in the spinal cord required to produce myelopathic changes using pH electrodes and a chemical microsensor. Studies will be completed during the grant year that were initiated in the last year on secondary changes in the rat spinal cord following Wallerian degeneration and postmortem autolysis which are being compared with the primary traumatic events and are critical to the interpretation of the latter. Future studies are anticipated which will determine the role of calcium in these secondary events, which are present in the traumatized spinal cord. In addition, freeze-fracture membrane pathological evaluation of spinal cord trauma will be initiated.